Acquired immune deficiency syndrome (AIDS) is a viral disease for which as yet there is no cure or effective vaccine. Patients with this disease have an immune system that is compromised through the destructive action of virus. This condition leaves the AIDS patient susceptible to opportunistic infections, caused by organisms which rarely cause disease in the healthy individual, but which are responsible for as much as 90% of the mortality of AIDS (Mills et al., Scientific American, 263, 50-57 (1986)). Many of these infections are caused by yeasts, which are single cell fungi. Fifty-eight to eighty-one percent of AIDS patients contract fungal infections (Holmberg et al., Scand. J. Infect. Dis., 18, 179-182 (1986)).
Candida albicans is the most common cause of fungal infection in AIDS patients. It produces candidal oropharyngitis (thrush), esophagitis, meningitis, and bronchial or pulmonary candidiasis (Id.). The source of the infection is assumed to be endogenous, probably from the intestine.
Cryptococcus neoformans is responsible for producing a severe meningitis, which is thought to arise from an initial infection of the lungs. The fungus invades the bloodstream and lodges in the meninges, the membrane covering the brain (Mills et al.,supra). C. neoformans spreads more readily than C. albicans beyond the skin and mucous membranes. It has a slippery outer coating that impedes macrophages and other immune cells, such as granulocytes, from ingesting the cryptococci (Id.) The coating also helps the fungi resist damage by enzymes from macrophages (Id.).
For the past 30 years, amphotericin B has been the only intravenous antifungal drug available for treating life-threatening fungal infections. It is still the most commonly used antifungal agent. It binds to ergosterol in the fungus' cell membrane. Amphotericin B damages the membrane and causes the internal contents of the fungus to leak out. However, amphotericin B also damages erythrocytes by binding to cholesterol in the cell membrane, causing anemia. Amphotericin B can also harm kidneys.
Because of these toxic effects, amphotericin B cannot be administered in dosages sufficiently high to kill invading fungi. Those patients who survive the disease must receive lifelong preventative therapy of intravenous treatments once or twice a week (Id.).
Fluconazole, an imidazole, has been proposed as an antifungal agent. It must be given orally, and its effectiveness has yet to be established. Fluorocytosine has been used in combination with amphotericin B. It is however, toxic to human cells. Thus, there is a dearth of effective antifungal agents. There is a great need to halt the large number of deaths which occur from opportunistic fungal infections which attack AIDS patients, cancer victims, organ transplant recipients, and other individuals having compromised immune systems.